AEGiS-14IAC: Genotypic (GT) and virtual phenotypic (vPT) correlates of virologic response to Abacavir (ABC)-based therapy in the ZORRO trial (ESS40009).

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Genotypic (GT) and virtual phenotypic (vPT) correlates of virologic response to Abacavir (ABC)-based therapy in the ZORRO trial (ESS40009).

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrB1386)

Ruane P, Hernandez J, Richmond G, Williams A, Fralich T, Yau L, Hessenthaler S, Lanier ER
Tower ID, LA, United States

BACKGROUND: Resistance testing may improve response in ART-experienced subjects. GT and PT testing have some utility in this setting. We tested the ability of the Virco GT and vPT to predict response to open-label ABC-based therapy in ART-experienced subjects.

METHODS: 833 ART-naïve and experienced subjects were treated in the US with ABC 300mg BID and ~ 2 other AR drugs, and followed for 16 weeks (wks). GT and vPT were done on ART-experienced subjects as per investigator discretion. Subjects with isolates susceptible to ABC and ~ 2 other AR drugs were enrolled. Changes in therapy were allowed as clinically indicated. Virologic responses (ITT, Observed analyses) were assessed at 8 and 16 wks and correlated with BL GT and vPT characteristics.

RESULTS: 180 subjects had GT and vPT performed. Median BL vRNA was 4.3 logs; median CD4 count was 315 cells/mm³. 98% of isolates had ~ 4 nucleoside-associated mutations and a vPT to ABC of < 4.5 fold compared to control virus (VFR). At Wk 8, median change in vRNA from BL was -1.38; median CD4 cell increase was 69, and the proportion of subjects with vRNA < 400 c/mL or ~ 1 log drop from BL was 71%. At Wk 16, median change in vRNA from BL was -1.33, median CD4 cell increase was 47 and the proportion of subjects with vRNA < 400 c/mL or ~ 1 log drop from BL was 65%. The table shows the proportion of subjects who achieved vRNA <400 c/mL or ~ 1 log drop from BL by BL resistance for ABC (and likely other NRTIs). *Note that all TAM categories are ± M184V. Notably, overall responses to these multi-switch regimens appeared to be predictable based on GT and vPT results. Additional analysis to include other variables will be presented.

CONCLUSIONS: ABC-based therapy, optimized by GT and vPT results, was effective for experienced subjects in clinical practice. [table: see text]

Keywords: AEGIS, Dideoxynucleosides, CD4 Lymphocyte Count, Antiretroviral Therapy, Highly Active, Drug Therapy, Combination, CD4-Positive T-Lymphocytes, Mutation, abacavir, virology, therapy, genetics, drug therapy

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ThOrB1386